Pluronic P85 enhances the efficacy of outer membrane vesicles as a subunit vaccine against Brucella melitensis challenge in mice

Authors

  • Neeta Jain-Gupta,

    1. Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Disease, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
    Search for more papers by this author
  • Araceli Contreras-Rodriguez,

    1. Departmento de Microbiologia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico, Mexico
    Search for more papers by this author
  • Ramesh Vemulapalli,

    1. Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
    Search for more papers by this author
  • Sharon G. Witonsky,

    1. Department of Large Animal Clinical Sciences, Center for Molecular Medicine and Infectious Disease, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
    Search for more papers by this author
  • Stephen M. Boyle,

    1. Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Disease, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
    Search for more papers by this author
  • Nammalwar Sriranganathan

    Corresponding author
    • Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Disease, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
    Search for more papers by this author

Correspondence: Nammalwar Sriranganathan, Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, 1410 Prices Fork Road, CMMID, Blacksburg, VA, 24061-0342, USA. Tel.: +1 540 231 7171; fax: +1 540 231 3426; e-mail: nathans@vt.edu

Abstract

Brucellosis is the most common zoonotic disease worldwide, and there is no vaccine for human use. Brucella melitensis Rev1, a live attenuated strain, is the commercial vaccine for small ruminants to prevent B. melitensis infections but has been associated with abortions in animals. Moreover, strain Rev1 is known to cause disease in humans and cannot be used for human vaccination. Outer membrane vesicles (OMVs) obtained from B. melitensis have been shown to provide protection similar to strain Rev1 in mice against B. melitensis challenge. In the present work, we tested the efficacy of Pluronic P85 as an adjuvant to enhance the efficacy of Brucella OMVs as a vaccine. P85 enhanced the in vitro secretion of TNF-α by macrophages induced with OMVs and P85. Further, P85 enhanced the protection provided by OMVs against B. melitensis challenge. This enhanced protection was associated with higher total IgG antibody production but not increased IFN-γ or IL-4 cytokine levels. Moreover, P85 alone provided significantly better clearance of B. melitensis compared to saline-vaccinated mice. Further studies are warranted to find the mechanism of action of P85 that provides nonspecific protection and enhances the efficacy of OMVs as a vaccine against B. melitensis.

Ancillary